Oligonucleotide directed site-specific mutagenesis is used to dissect the biochemical basis of oncogenic activation and of enzymatic activity of the ras oncogene. Studies are directed toward an understanding of the interrelationship between the known properties of the ras gene product, p21. These include guanine nucleotide binding, GTP hydrolysis activity, and an autokinase activity ras protein. Mutagenesis of the ras oncogene in the specific regions of the protein have been designed to explore the active center which is believed to be responsible for these properties. It has been shown that replacement of the phosphoryl acceptor in p21 has a profound effect on GTPase activity and GTP binding. Mutations have also been created to study the role of GTP binding in oncogenicity.